MicroRNA-responsive release of Cas9/sgRNA from DNA nanoflower for cytosolic protein delivery and enhanced genome editing

【作者】Jinjin Shi, Xue Yang, Yanan Li, Danyu Wang, Wei Liu, Zhenzhong, Zhang, Junjie Liu*, Kaixiang Zhang*

【期刊名】 Biomaterials

【影响因子】 10.317

【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

【年，卷(期)：页码】2020, 256, 120221

【关键词】 CRISPR/Cas9DNA nanoflowermiRNA-responsivecytosolic deliverygenome editing

【摘要】Nanoparticle-based CRISPR/Cas9 delivery systems hold great promise for specific and precise treatment of genetic disorder diseases. Herein, we developed a DNA nanoflower-based platform for microRNA-responsive cytosolic delivery of Cas9/sgRNA complex into tumor cells. The biocompatible DNA nano-vehicles can efficiently load Cas9/sgRNA by sequence hybridization. Importantly, this hybridization can be replaced by a tumor specific miRNA through toehold-mediated strand displacement process and achieve cell-type-specific release of Cas9/sgRNA from the DNA nanoflowers. We have verified that this miRNA-responsive releasing process can significantly improve the genome editing efficiency comparing with non-responsive control. This strategy suggests a versatile way for designing more specific and efficient CRISPR-based genome therapy system by incorporating stimuli-responsive Cas9/sgRNA release process.

【全文链接】https://www.sciencedirect.com/science/article/pii/S0142961220304671